Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen. Several antibiotic resistant strains of P. aeruginosa are commonly found as secondary infection in immune-compromised patients leaving significant mortality and healthcare cost. Pseudomonas aeruginosa successfully avoids the process of phagocytosis, the first line of host defense, by secreting several toxic effectors. Effectors produced from P. aeruginosa Type III secretion system are critical molecules required to disrupt mammalian cell signaling and holds particular interest to the scientists studying host-pathogen interaction. Exoenzyme S (ExoS) is a bi-functional Type III effector that ADP-ribosylates several intracellular Ras (Rat sarcoma) and Rab (Response to abscisic acid) small GTPases in targeted host cells. The Rab5 protein acts as a rate limiting protein during phagocytosis by switching from a GDP- bound inactive form to a GTP-bound active form. Activation and inactivation of Rab5 protein is regulated by several Rab5-GAPs (GTPase Activating Proteins) and Rab5-GEFs (Rab5-Guanine nucleotide Exchange Factors). Some pathogenic bacteria have shown affinity for Rab proteins during infection and make their way inside the cell. This dissertation demonstrated that Rab5 plays a critical role during early steps of P. aeruginosa invasion in J774-Eclone macrophages. It was found that live, but not heat inactivated, P. aeruginosa inhibited phagocytosis that occurred in conjunction with down-regulation of Rab5 activity. Inactivation of Rab5 was dependent on ExoS ADP-ribosyltransferase activity, and more than one arginine sites in Rab5 are possible targets for ADP-ribosylation modification. However, the expression of Rin1, but not other Rab5GEFs (Rabex-5 and Rap6) reversed this down-regulation of Rab5 in vivo. Further studies revealed that the C-terminus of Rin1 carrying Rin1:Vps9 and Rin1:RA domains are required for optimal Rab5 activation in conjunction with active Ras. These observations demonstrate a novel mechanism of Rab5 targeting to phagosome via Rin1 during the phagocytosis of P. aeruginosa. The second part of this dissertation investigated antimicrobial activities of Dehydroleucodine (DhL), a secondary metabolite from Artemisia douglasiana, against P. aeruginosa growth and virulence. Populations of several P. aeruginosa strains were completely susceptible to DhL at a concentration between 0.48~0.96 mg/ml and treatment at a threshold concentration (0.12 mg/ml) inhibited growth and many virulent activities without damaging the integrity of the cell suggesting anti-Pseudomonas activity of DhL.

Is socioeconomic position early in life associated with physical activity during adulthood following the accumulation of risk model with additive effects?

L'activité physique améliore la santé, mais seulement 4.8% des Canadiens atteignent le niveau recommandé. La position socio-économique est un des déterminants de l'activité physique les plus importants. Elle est associée à l’activité physique de manière transversale à l’adolescence et à l’âge adulte. Cette thèse a tenté de déterminer s'il y a une association à long terme entre la position socio-économique au début du parcours de vie et l’activité physique à l’âge adulte. S'il y en avait une, un deuxième objectif était de déterminer quel modèle théorique en épidémiologie des parcours de vie décrivait le mieux sa forme. Cette thèse comprend trois articles: une recension systématique et deux recherches originales. Dans la recension systématique, des recherches ont été faites dans Medline et EMBASE pour trouver les études ayant mesuré la position socio-économique avant l'âge de 18 ans et l'activité physique à ≥18 ans. Dans les deux recherches originales, la modélisation par équations structurelles a été utilisée pour comparer trois modèles alternatifs en épidémiologie des parcours de vie: le modèle d’accumulation de risque avec effets additifs, le modèle d’accumulation de risque avec effet déclenché et le modèle de période critique. Ces modèles ont été comparés dans deux cohortes prospectives représentatives à l'échelle nationale: la 1970 British birth cohort (n=16,571; première recherche) et l’Enquête longitudinale nationale sur les enfants et les jeunes (n=16,903; deuxième recherche). Dans la recension systématique, 10 619 articles ont été passés en revue par deux chercheurs indépendants et 42 ont été retenus. Pour le résultat «activité physique» (tous types et mesures confondus), une association significative avec la position socio-économique durant l’enfance fut trouvée dans 26/42 études (61,9%). Quand seulement l’activité physique durant les loisirs a été considérée, une association significative fut trouvée dans 21/31 études (67,7%). Dans un sous-échantillon de 21 études ayant une méthodologie plus forte, les proportions d’études ayant trouvé une association furent plus hautes : 15/21 (71,4%) pour tous les types et toutes les mesures d’activité physique et 12/15 (80%) pour l’activité physique de loisir seulement. Dans notre première recherche originale sur les données de la British birth cohort, pour la classe sociale, nous avons trouvé que le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux chez les hommes et les femmes pour l’activité physique de loisir, au travail et durant les transports. Dans notre deuxième recherche originale sur les données canadiennes sur l'activité physique de loisir, nous avons trouvé que chez les hommes, le modèle de période critique s’est ajusté le mieux aux données pour le niveau d’éducation et le revenu, alors que chez les femmes, le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux pour le revenu, tandis que le niveau d’éducation ne s’est ajusté à aucun des modèles testés. En conclusion, notre recension systématique indique que la position socio-économique au début du parcours de vie est associée à la pratique d'activité physique à l'âge adulte. Les résultats de nos deux recherches originales suggèrent un patron d’associations le mieux représenté par le modèle d’accumulation de risque avec effets additifs.

Commandeering Aesop’s Bamboo Canon: A 19th Century Confederacy of Creole Fugitive Fables

In my thesis, “Commandeering Aesop’s Bamboo Canon: A 19th Century Confederacy of Creole Fugitive Fables,” I ask and answer the ‘Who? What? Where? When? Why?” of Creole Literature using the 19th century production of Aesopian fables as clues to resolve a set of linguistic, historical, literary, and geographical enigmas pertaining the ‘birth-place(s)’ of Creolophone Literatures in the Caribbean Sea, North and South America, as well as the Indian Ocean. Focusing on the fables in Martinique (1846), Reunion Island (1826), and Mauritius (1822), my thesis should read be as an attempt capture the links between these islands through the creation of a particular archive defined as a cartulary-chronicle, a diplomatic codex, or simply a map in which I chart and trace the flight of the founding documents relating to the lives of the individual authors, editors, and printers in order to illustrate the articulation of a formal and informal confederation that enabled the global and local institutional promotion of Creole Literature. While I integrate various genres and multi-polar networks between the authors of this 19th century canon comprised of sacred and secular texts such as proclamations, catechisms, and proverbs, the principle literary genre charted in my thesis are collections of fables inspired by French 17th century French Classical fabulist, Jean de la Fontaine. Often described as the ‘matrix’ of Creolophone Literature, these blues and fables constitute the base of the canon, and are usually described as either ‘translated,’ ‘adapted,’ and even ‘cross-dressed’ into Creole in all of the French Creolophone spaces. My documentation of their transnational sprouting offers proof of an opaque canonical formation of Creole popular literature. By constituting this archive, I emphasize the fact that despite 200 years of critical reception and major developments and discoveries on behalf of Creole language pedagogues, literary scholars, linguists, historians, librarians, archivist, and museum curators, up until now not only have none have curated this literature as a formal canon. I also offer new empirical evidence in order to try and solve the enigma of “How?” the fables materially circulated between the islands, and seek to come to terms with the anonymous nature of the texts, some of which were published under pseudonyms. I argue that part of the confusion on the part of scholars has been the result of being willfully taken by surprise or defrauded by the authors, or ‘bamboozled’ as I put it. The major paradigmatic shift in my thesis is that while I acknowledge La Fontaine as the base of this literary canon, I ultimately bypass him to trace the ancient literary genealogy of fables to the infamous Aesop the Phrygian, whose biography – the first of a slave in the history of the world – and subsequent use of fables reflects a ‘hidden transcript’ of ‘masked political critique’ between ‘master and slave classes’ in the 4th Century B.C.E. Greece.

This archive draws on, connects and critiques the methodologies of several disciplinary fields. I use post-colonial literary studies to map the literary genealogies Aesop; use a comparative historical approach to the abolitions of slavery in both the 19th century Caribbean and the Indian Ocean; and chart the early appearance of folk music in early colonial societies through Musicology and Performance Studies. Through the use of Sociolinguistics and theories of language revival, ecology, and change, I develop an approach of ‘reflexive Creolistics’ that I ultimately hope will offer new educational opportunities to Creole speakers. While it is my desire that this archive serves linguists, book collectors, and historians for further scientific inquiry into the innate international nature of Creole language, I also hope that this innovative material defense and illustration of Creole Literature will transform the consciousness of Creolophones (native and non-native) who too remain ‘bamboozled’ by the archive. My goal is to erase the ‘unthinkability’ of the existence of this ancient maritime creole literary canon from the collective cultural imaginary of readers around the globe.

RELIGIOUS SCULPTURE OF THE CHILOÉ ARCHIPELAGO, FROM THE 17TH TO THE 21ST CENTURY

Despite its central role in religious life of the region, the sculptural tradition of the Southern Chilean Chiloé Archipelago, ranging from the 17th century to the present day, has been vastly understudied. Isidoro Vázquez de Acuña’s 1994 volume Santeria de Chiloe: ensayo y catastro remains the only catalogue of Chilote sculpture. Though the author includes photographs of a vast array of works, he does not attempt to place the sculptures within a chronology, or consider their place within the greater Latin American context. My thesis will place this group of works within a chronological and geographical context that reaches from the 16th century to the present day, connected to the artistic traditions of regions as far afield as Paraguay and Lima. I will first consider the works brought to the Archipelago by religious orders – the Jesuits and Franciscans – as well as influences on artistic style and religious culture throughout the 17th, 18th and 19th centuries. I will focus in particular on three works generally considered to be from the 17th and 18th centuries – the Virgin of Loreto at Achao, the Saint Michael at Castro, and the Jesus Nazareno of Caguach – using visual analysis and sifting through generations of primary and secondary sources to determine from where and when these sculptures came. With this investigation as a foundation, I will consider how they inspired vernacular sculptural expression and trace ‘family trees’ of vernacular works based on these precedents. Vernacular artistic traditions are often viewed as derivative and lacking in skill, but Chilote sculptors in fact engaged with a variety of outside influences and experimented with different sculptural styles. I will conclude by considering which aspects of these styles Chilote artists chose to incorporate into their own work, alter or exclude, artistic decisions that shed light on the Archipelago’s religious and cultural fabric.

Factors influencing the radiative surface temperature of grey seal (Halichoerus grypus) pups during early and late lactation

The aim of this study was to examine the variation in body surface temperature of grey seal (Halichoerus grypus) pups throughout lactation in response to different environmental conditions. Radiative surface temperatures (T r, °C) of pups were measured on the Isle of May (56°11′N, 02°33′W), southeast Scotland from 29 October to 25 November 2003. Records were obtained from a total of 60 pups (32 female and 28 male) from three different pupping sites during early and late lactation. Pups were sheltered from high wind speeds but air temperature, humidity and solar radiation at pupping sites were similar to general meteorological conditions. The mean T r of all pups was 15.8°C (range 7.7–29.7°C) at an average air temperature of 10.2°C (range 6.5–13.8°C). There was no difference in the mean T r of pups between early and late lactation. However, the T r varied between different regions of the body with hind flippers on average 2–6°C warmer than all other areas measured. There was no difference in mean T r of male and female pups and pup body mass did not account for the variation in T r during early or late lactation. Throughout the day there was an increase in the T r of pups and this explained 20–28% of the variation in T r depending on stage of lactation. There was no difference in the mean T r of pups between pupping sites or associated with different substrate types. Wind speed and substrate temperature had no effect on the T r of pups. However, solar radiation, air temperature and relative humidity accounted for 48% of the variation in mean T r of pups during early lactation. During late lactation air temperature and solar radiation alone accounted for 43% of the variation in T r. These results indicate that environmental conditions explain only some of the variation in T r of grey seal pups in natural conditions. Differences in T r however indicate that the cost of thermoregulation for pups will vary throughout lactation. Further studies examining intrinsic factors such as blubber thickness and activity levels are necessary before developing reliable biophysical models for grey seals.

Health assets and active lifestyles during preadolescence and adolescence: highlights from the HBSC/WHO health survey and implications for health promotion

The present chapter discusses the assets model as a theoretical approach to the study of health behavior and health promotion. The model emphasizes people’s talents, competences, and resources. In this chapter, a health asset is defined as any factor or resource that maximizes the opportunities for individuals, local communities, and populations to attain and maintain health and well-being. This perspective expands and complements the current medical model as it focuses on the development of a sense of empowerment in community members to prevent and manage their own health. Therefore, in this chapter we address the concepts of salutogenesis, social support, resilience, coping, self-regulation, social capital, and personal and social competence, which are central to the development of individuals’ potential to manage and savor their own health, creating the conditions for self-fulfillment. Additionally, we demonstrate how the assets model guides the study of children’s and adolescents’ health in the Portuguese Health Behaviour in School-aged Children study (www.hbsc.org), concentrating on areas such as active lifestyles and quality-of-life perception. Finally, we present a roadmap for action that emphasizes the need to identify the factors that make children and adolescents happy and healthy individuals, while minimizing risks and problems they naturally encounter throughout their development. We also argue for the need to involve young people in discussions concerning their health and health promotion practices, focusing on the development of talents, capabilities, and positive expectations for the future.

Unexpected Levels of Biological Activity during the Polar Night Offer New Perspectives on a Warming Arctic

The current understanding of Arctic ecosystems is deeply rooted in the classical view of a bottom-up controlled system with strong physical forcing and seasonality in primary-production regimes. Consequently, the Arctic polar night is commonly disregarded as a time of year when biological activities are reduced to a minimum due to a reduced food supply. Here, based upon a multidisciplinary ecosystem-scale study from the polar night at 79 degrees N, we present an entirely different view. Instead of an ecosystem that has entered a resting state, we document a system with high activity levels and biological interactions across most trophic levels. In some habitats, biological diversity and presence of juvenile stages were elevated in winter months compared to the more productive and sunlit periods. Ultimately, our results suggest a different perspective regarding ecosystem function that will be of importance for future environmental management and decision making, especially at a time when Arctic regions are experiencing accelerated environmental change [1].

Comprehensive economic and financial analysis of the enterprise activity: approaches, methods and implementation

This thesis intends to analyse the performance and the efficiency of companies and to identify the key factors that may explain it. A comprehensive analysis based on a set of economic and financial ratios was studied as an instrument which provides information on enterprise performance and its efficiency. It was selected a sample with 15 enterprises: 7 Portuguese and 8 Ukrainian ones, belonging to several industries. Financial and non-financial data was collected for 6 years, during the period of 2009 to 2014. Research questions that guided this work were: Are the enterprises efficient/profitable? What factors influence enterprises’ efficiency/performance? Is there any difference between Ukrainian and Portuguese enterprises’ efficiency/performance, which factors have more influence? Which industrial sector is represented by more efficient/profitable enterprises? The main results showed that in average enterprises were efficient; comparing by states Ukrainian enterprises are more efficient; industries have similar level of efficiency. Among factors that influence ATR positively are fixed and current assets turnover ratios, ROA; negatively influencing are EBITDA margin and liquidity ratio. There is no significant difference between models by country. Concerning profitability, enterprises have low performance level but in comparison of countries Ukrainian enterprises have better profitability in average. Regarding the industry sector, paper industry is the most profitable. Among factors influencing ROA are profit margin, fixed asset turnover ratio, EBITDA margin, Debt to equity ratio and the country. In case of profitability both countries have different models. For Ukrainian enterprises is suggested to pay attention on factors of Short-term debt to total debt, ROA, Interest coverage ratio in order to be more efficient; Profit margin and EBITDA margin to make their performance better. For Portuguese enterprises for improving efficiency the observation and improvement of fixed assets turnover ratio, current assets turnover ratio, Short-term financial debt to total debt, Leverage Ratio, EBITDA margin is suggested; for improving higher profitability track fixed assets turnover ratio, current assets turnover ratio, Debt to equity ratio, Profit margin and Interest coverage ratio is suggested.

Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy

Importance A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. Objective To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. Design, Setting, and Participants The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. Exposures Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. Main Outcomes and Measures Risk of within-couple HIV transmission to the HIV-negative partner. Results Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22 000 condomless sex acts and heterosexuals approximately 36 000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. Conclusions and Relevance Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.

The Effect Of Celastrol, A Triterpene With Antitumorigenic Activity, On Conformational And Functional Aspects Of The Human 90kda Heat Shock Protein Hsp90α, A Chaperone Implicated In The Stabilization Of The Tumor Phenotype.

Hsp90 is a molecular chaperone essential for cell viability in eukaryotes that is associated with the maturation of proteins involved in important cell functions and implicated in the stabilization of the tumor phenotype of various cancers, making this chaperone a notably interesting therapeutic target. Celastrol is a plant-derived pentacyclic triterpenoid compound with potent antioxidant, anti-inflammatory and anticancer activities; however, celastrol's action mode is still elusive. In this work, we investigated the effect of celastrol on the conformational and functional aspects of Hsp90α. Interestingly, celastrol appeared to target Hsp90α directly as the compound induced the oligomerization of the chaperone via the C-terminal domain as demonstrated by experiments using a deletion mutant. The nature of the oligomers was investigated by biophysical tools demonstrating that a two-fold excess of celastrol induced the formation of a decameric Hsp90α bound throughout the C-terminal domain. When bound, celastrol destabilized the C-terminal domain. Surprisingly, standard chaperone functional investigations demonstrated that neither the in vitro chaperone activity of protecting against aggregation nor the ability to bind a TPR co-chaperone, which binds to the C-terminus of Hsp90α, were affected by celastrol. Celastrol interferes with specific biological functions of Hsp90α. Our results suggest a model in which celastrol binds directly to the C-terminal domain of Hsp90α causing oligomerization. However, the ability to protect against protein aggregation (supported by our results) and to bind to TPR co-chaperones are not affected by celastrol. Therefore celastrol may act primarily by inducing specific oligomerization that affects some, but not all, of the functions of Hsp90α. To the best of our knowledge, this study is the first work to use multiple probes to investigate the effect that celastrol has on the stability and oligomerization of Hsp90α and on the binding of this chaperone to Tom70. This work provides a novel mechanism by which celastrol binds Hsp90α.

Antioxidant Activity Of Hydrophilic And Lipophilic Extracts Of Brazilian Blueberries.

Hydrophilic and lipophilic extracts of ten cultivars of Highbush and Rabbiteye Brazilian blueberries (Vaccinium corymbosum L. and Vacciniumashei Reade, respectively) that are used for commercial production were analysed for antioxidant activity by the FRAP, ORAC, ABTS and β-carotene-linoleate methods. Results were correlated to the amounts of carotenoids, total phenolics and anthocyanins. Brazilian blueberries had relatively high concentration of total phenolics (1,622-3,457 mg gallic acid equivalents per 100 g DW) and total anthocyanins (140-318 mg cyanidin-3-glucoside equivalents per 100 g DW), as well as being a good source of carotenoids. There was a higher positive correlation between the amounts of these compounds and the antioxidant activity of hydrophilic compared to lipophilic extracts. There were also significant differences in the level of bioactive compounds and antioxidant activities between different cultivars, production location and year of cultivation.

Effects Of High Pressure Homogenization On The Activity, Stability, Kinetics And Three-dimensional Conformation Of A Glucose Oxidase Produced By Aspergillus Niger.

High pressure homogenization (HPH) is a non-thermal method, which has been employed to change the activity and stability of biotechnologically relevant enzymes. This work investigated how HPH affects the structural and functional characteristics of a glucose oxidase (GO) from Aspergillus niger. The enzyme was homogenized at 75 and 150 MPa and the effects were evaluated with respect to the enzyme activity, stability, kinetic parameters and molecular structure. The enzyme showed a pH-dependent response to the HPH treatment, with reduction or maintenance of activity at pH 4.5-6.0 and a remarkable activity increase (30-300%) at pH 6.5 in all tested temperatures (15, 50 and 75°C). The enzyme thermal tolerance was reduced due to HPH treatment and the storage for 24 h at high temperatures (50 and 75°C) also caused a reduction of activity. Interestingly, at lower temperatures (15°C) the activity levels were slightly higher than that observed for native enzyme or at least maintained. These effects of HPH treatment on function and stability of GO were further investigated by spectroscopic methods. Both fluorescence and circular dichroism revealed conformational changes in the molecular structure of the enzyme that might be associated with the distinct functional and stability behavior of GO.

Beliefs And Misbeliefs About Current Interventions During Labor And Delivery In Brazil.

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Ankhd1 Silencing Inhibits Stathmin 1 Activity, Cell Proliferation And Migration Of Leukemia Cells.

ANKHD1 is highly expressed in human acute leukemia cells and potentially regulates multiple cellular functions through its ankyrin-repeat domains. In order to identify interaction partners of the ANKHD1 protein and its role in leukemia cells, we performed a yeast two-hybrid system screen and identified SIVA, a cellular protein known to be involved in proapoptotic signaling pathways. The interaction between ANKHD1 and SIVA was confirmed by co-imunoprecipitation assays. Using human leukemia cell models and lentivirus-mediated shRNA approaches, we showed that ANKHD1 and SIVA proteins have opposing effects. While it is known that SIVA silencing promotes Stathmin 1 activation, increased cell migration and xenograft tumor growth, we showed that ANKHD1 silencing leads to Stathmin 1 inactivation, reduced cell migration and xenograft tumor growth, likely through the inhibition of SIVA/Stathmin 1 association. In addition, we observed that ANKHD1 knockdown decreases cell proliferation, without modulating apoptosis of leukemia cells, while SIVA has a proapoptotic function in U937 cells, but does not modulate proliferation in vitro. Results indicate that ANKHD1 binds to SIVA and has an important role in inducing leukemia cell proliferation and migration via the Stathmin 1 pathway. ANKHD1 may be an oncogene and participate in the leukemia cell phenotype.

Increased Expression Of Hes5 Protein In Notch Signaling Pathway In The Hippocampus Of Mice Offspring Of Dams Fed A High-fat Diet During Pregnancy And Suckling.

Maternal high-fat diet (HFD) impairs hippocampal development of offspring promoting decreased proliferation of neural progenitors, in neuronal differentiation, in dendritic spine density and synaptic plasticity reducing neurogenic capacity. Notch signaling pathway participates in molecular mechanisms of the neurogenesis. The activation of Notch signaling leads to the upregulation of Hes5, which inhibits the proliferation and differentiation of neural progenitors. This study aimed to investigate the Notch/Hes pathway activation in the hippocampus of the offspring of dams fed an HFD. Female Swiss mice were fed a control diet (CD) and an HFD from pre-mating until suckling. The bodyweight and mass of adipose tissue in the mothers and pups were also measured. The mRNA and protein expression of Notch1, Hes5, Mash1, and Delta1 in the hippocampus was assessed by RT-PCR and western blotting, respectively. Dams fed the HFD and their pups had an increased bodyweight and amount of adipose tissue. Furthermore, the offspring of mothers fed the HFD exhibited an increased Hes5 expression in the hippocampus compared with CD offspring. In addition, HFD offspring also expressed increased amounts of Notch1 and Hes5 mRNA, whereas Mash1 expression was decreased. However, the expression of Delta1 did not change significantly. We propose that the overexpression of Hes5, a Notch effector, downregulates the expression of the proneural gene Mash1 in the offspring of obese mothers, delaying cellular differentiation. These results provide further evidence that an offspring's hippocampus is molecularly susceptible to maternal HFD and suggest that Notch1 signaling in this brain region is important for neuronal differentiation.